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Impact of autism genetic risk on cortical sensorimotor dynamics

Award Number: F32MH130163
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Impact of autism genetic risk on cortical sensorimotor dynamics - Project Summary Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder defined by social deficits and restricted and repetitive behaviors. These behaviors have been associated with impaired sensory processing and sensorimotor integration. In addition, ASD is often comorbid with intellectual disability (ID) and cognitive impairment. This is especially true of ASD diagnoses associated with one of several major ASD risk genes. While it is well established that sensory processing is critical for cognitive function in general and learning in particular, it is not clear how deficits in sensory processing in ASD may contribute to cognitive and learning impairments in patients. I hypothesize that learning impairments in ASD patients stem from sensory processing deficits leading to a disruption in cortical functional connectivity critical for learned behaviors. I will test this idea by using a mouse model of major ASD genetic risk that shows a tactile instrumental learning impairment. Importantly, learning deficits require the function of the ASD risk gene in cortical excitatory projection neurons (see preliminary data) highlighting the importance for cortical processing in this phenotype. In addition, these animals have a reduced cortical response to touch. In Aim 1, I will assess the impact of the ASD risk gene on sensory processing in dorsal cortex by monitoring calcium dynamics as mice receive passive sensory stimulation. In addition, I will manipulate the ASD risk gene in sensory cortex to test its autonomous control of calcium dynamics and connectivity. I expect that the ASD risk gene model mice will have reduced responses in sensory cortex and disrupted functional connectivity to downstream regions in dorsal cortex. In Aim 2, I will monitor dorsal cortex calcium dynamics as mice perform an instrumental learning task to test the idea that the major ASD risk gene causes altered dynamics of cortical functional connectivity. Furthermore, I will determine to what extent putative mesoscale connectivity deficits in the mouse model predict learning impairments in the task. Lastly, I will specifically manipulate the ASD risk gene in sensory cortex to tests its autonomous role in regulating functional connectivity during learning. The impact of this proposal will be to understand the neurobiological underpinnings of impaired learning related to a major ASD risk gene, which may serve to inform the development of treatments for cognitive deficits in ASD patients. In conclusion, I am an excellent candidate for a National Research Service Award Fellowship because of my background in ASD risk gene research and the training in cutting-edge systems neuroscience tools provided by the Rumbaugh lab. Altogether, the training and experiments proposed here will enable me to further our understanding of ASD and lay a strong foundation for my career goal of running an independent research laboratory.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $86,224 )
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	000	2	11/25/2024	SUPPLEMENT FOR EXPANSION	$3,000
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	001	3	6/25/2025	NON-COMPETING CONTINUATION	$83,224
														Subtotal = $86,224

Issue Date FY: 2024 ( Subtotal = $76,756 )
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	000	2	6/17/2024	NON-COMPETING CONTINUATION	$76,756
														Subtotal = $76,756

Issue Date FY: 2023 ( Subtotal = $69,500 )
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	001	1	5/30/2023	NEW	$0
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	000	1	5/30/2023	NEW	$69,500
														Subtotal = $69,500

Grand Total All Awards = $232,480

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Impact of autism genetic risk on cortical sensorimotor dynamics

Award Number: F32MH130163

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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